Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2001-1-26
pubmed:abstractText
In this review, we argue that at least one insult that causes Alzheimer's disease (AD) is disruption of the normal function of the amyloid precursor protein (APP). Familial Alzheimer's disease (FAD) mutations in APP cause a disease phenotype that is identical (with the exception that they cause an earlier onset of the disease) to that of 'sporadic' AD. This suggests that there are molecular pathways common to FAD and sporadic AD. In addition, all individuals with Down syndrome, who carry an extra copy of chromosome 21 and overexpress APP several-fold in the brain, develop the pathology of AD if they live past the age of 40. These data support the primacy of APP in the disease. Although APP is the source of the beta-amyloid (Abeta) that is deposited in amyloid plaques in AD brain, the primacy of APP in AD may not lie in the production of Abeta from this molecule. We suggest instead that APP normally functions in the brain as a cell surface signaling molecule, and that a disruption of this normal function of APP is at least one cause of the neurodegeneration and consequent dementia in AD. We hypothesize in addition that disruption of the normal signaling function of APP causes cell cycle abnormalities in the neuron, and that these abnormalities constitute one mechanism of neuronal death in AD. Data supporting these hypotheses have come from investigations of the molecular consequences of neuronal expression of FAD mutants of APP or overexpression of wild type APP, as well as from identification of binding proteins for the carboxyl-terminus (C-terminus) of APP.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
886
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
54-66
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Alzheimer's disease: a dysfunction of the amyloid precursor protein(1).
pubmed:affiliation
Department of Psychiatry, Harvard Medical School, MRC 223 McLean Hospital, 115 Mill St., 02478, Belmont, MA, USA. neve@helix.mgh.harvard.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review